Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis

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dc.article.numbere0177472
dc.catalogadorpva
dc.contributor.authorPardo, Evelyn
dc.contributor.authorCárcamo, Claudia
dc.contributor.authorUribe-San Martín, Reinaldo
dc.contributor.authorCiampi, Ethel
dc.contributor.authorSegovia-Miranda, Fabián
dc.contributor.authorCurkovic-Peña, Cristobal
dc.contributor.authorMontecino, Fabián
dc.contributor.authorHolmes, Christopher
dc.contributor.authorTichauer, Juan Enrique
dc.contributor.authorAcuña, Eric
dc.contributor.authorOsorio-Barrios, Francisco
dc.contributor.authorCastro, Marjorie
dc.contributor.authorCortes, Priscilla
dc.contributor.authorOyanadel, Claudia
dc.contributor.authorValenzuela, David M.
dc.contributor.authorPacheco, Rodrigo
dc.contributor.authorNaves, Rodrigo
dc.contributor.authorSoza, Andrea
dc.contributor.authorGonzález, Alfonso
dc.date.accessioned2024-01-19T18:21:47Z
dc.date.available2024-01-19T18:21:47Z
dc.date.issued2017
dc.description.abstractGalectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.
dc.fechaingreso.objetodigital2024-04-12
dc.fuente.origenORCID-ene24
dc.identifier.doi10.1371/journal.pone.0177472
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0177472
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80787
dc.information.autorucEscuela de Medicina; Ciampi Diaz, Ethel Leslie; 0000-0002-7330-5433; 132794
dc.issue.numero6
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final26
dc.pagina.inicio1
dc.revistaPLoS ONE
dc.rightsacceso abierto
dc.rights.licenseCC BY 4.0 DEED Attribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleGalectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis
dc.typeartículo
dc.volumen12
sipa.codpersvinculados132794
sipa.trazabilidadORCID;2024-01-08
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